[Significance of the thymus gland in internal medicine].
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Adolescent↗
Biomedical subjects
M Tsuchiya
Publications and source records attributed to M Tsuchiya.
[Interrelation between the thymus and the other endocrine glands].
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Adrenal Glands↗
Indole alkaloids in medicine.
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Alkaloids↗
A novel endotoxin-specific assay by turbidimetry with Limulus amoebocyte lysate containing beta-glucan.
The gelation of standard Limulus amoebocyte lysate (LAL) is triggered by the addition of a small amount of beta-glucan (1-1000 ng/ml plasma), but in the presence of an excessive amount of beta-glucan (1 mg/ml plasma), the gelation becomes insensitive to beta-glucan. Utilizing this property, a method to determine quantitatively the amount of endotoxin circulating in humans was developed. When a modified LAL, or LAL-ES, which contains an excessive amount of CM-curdlan as beta-glucan, was used for the assay, a linear relation in the logarithmic scales was obtained between the gelation time measured by the turbidimetry (min) and the concentration of endotoxin. This relation was not affected by a considerable amount of beta-glucan (100 ng/ml). The sensitivity of the endotoxin assay was estimated to be as low as 3 pg/ml. The following aspects of the method were found by clinical application to normal and febrile subjects. (1) Using both LAL and LAL-ES, it was possible to distinguish the effect of endotoxin from that of beta-glucan in plasma, i.e., bacterial sepsis from fungal sepsis. (2) The amount of circulating endotoxin determined by the present method showed good correlation to those obtained by chromogenic assay using modified LAL devoid of Factor G which could be activated by beta-glucan.
Endotoxins↗
Autoradiographic demonstration of gastrin binding sites in rat gastric mucosa.
The location of 125I-iodotyrosyl gastrin I binding sites in rat gastric mucosa was studied. Peptide specificity was demonstrated by competitive binding studies through the addition of a large dose of cold human gastrin I or cholecystokinin-octapeptide. Autoradiography of the stomach tissue was carried out by freeze-drying, embedding in Epon, wet-sectioning with ethylene glycol, and dry-mounting the emulsion film by means of the wire-loop method to prevent loss of the labeled substance. Specific binding sites for gastrin were found on parietal and chief cells, whereas few binding sites were seen on the surface mucous or mucous neck cells. Binding sites on the parietal cells were dispersed in the cytoplasm, while those on the chief cells were found near the basal plasma membrane.
Animals↗
Alcohol dehydrogenase: a new sensitive marker of hepatic centrilobular damage.
To determine whether serum alcohol dehydrogenase (ADH) activity reflects hepatic damage of centrilobular region (zone 3), the rats were given either bromobenzene (BB) or allyl alcohol (AA) IP to produce the pericen tral or periportal necrosis respectively. After AA or BB serum alanine aminotransferase (ALT) activity showed no significant difference between the two groups. By contrast, serum ADH and glutamate dehydrogenase (GLDH) activities were elevated preferentially in the BB treated rats. However, AA administration to rats also resulted in a significant increase in GLDH activity, whereas ADH activity was only slightly elevated when compared to controls. Moreover, acute ethanol administration to rats resulted in a significant elevation of the serum ADH activity, whereas serum GLDH and ALT activities remained normal. These data suggest that serum ADH activity appears to be a sensitive and specific marker of hepatic centrilobular damage.
1-Propanol↗
Mild but prolonged elevation of serum angiotensin converting enzyme (ACE) activity in alcoholics.
Serum activity of angiotensin converting enzyme (ACE) was serially measured in 47 hospitalized chronic alcoholics with liver disease. Compared to healthy controls, ACE activity, on admission, in the serum of alcoholics was significantly elevated (42.5 +/- 16.6 U/ml vs. 32.4 +/- 9.6 U/ml; p less than 0.005). About 36% of the patients had an elevated ACE level exceeding an upper normal value of 42 U/ml (mean +/- SD). In contrast to the rapid normalization of such enzymes as aspartate transaminase (AST), alanine transaminase (ALT) and lactic dehydrogenase (LDH) which represent parenchymal liver cell injury, the activity of ACE remained elevated over a period of 4 weeks even with abstinence. The serum level of ACE was significantly correlated with levels of alkaline phosphatase, gamma-glutamyltranspeptidase and monoamine oxidase, but not with those of AST, ALT and LDH. These data suggest increased ACE activity in alcoholics may be related to the influence of chronic consumption of alcohol on hepatic nonparenchymal systems.
Adult↗
Increase in mitochondrial GOT (m-GOT) activity after chronic alcohol consumption: clinical and experimental observations.
In order to clarify the origin and the mechanism of increased serum activity of glutamic oxalacetic transaminase (GOT) in chronic alcoholics, clinical and experimental investigations were carried out. Mitochondrial (m-GOT) and cytosolic GOT (c-GOT) isoenzymes were separated chromatographically by using a mini-column packed with Sephadex A50. Sixty percent of 63 alcoholics had elevated serum GOT. The m-GOT activity in alcoholics with total serum GOT activity of over 50 Karmen Units was 17.2 +/- 1.6 K.U. and the m-GOT/GOT ratio was the highest when compared to those in non-alcoholic liver diseases. In in vitro study, six hours of incubation of isolated hepatocytes from rats fed ethanol chronically resulted in an increased leakage of m-GOT into the incubation medium and also showed a tendency of a higher m-GOT/GOT ratio than that from control rats. The m-GOT activity thus released into the medium showed a highly significant inverse correlation with the viability of hepatocytes. These data suggest that m-GOT substantially contributes to an increased serum GOT often observed in chronic alcoholics.
Alcoholism↗
Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor.
Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of hormone-like glycoproteins that regulate haematopoietic cell proliferation and differentiation, and G-CSF almost exclusively stimulates the colony formation of granulocytes from committed precursor cells in semi-solid agar culture. Recently, Nomura et al. have established a human squamous carcinoma cell line (designated CHU-2) from a human oral cavity tumour which produces large quantities of CSF constitutively, and the CSF produced by CHU-2 cells has been purified to homogeneity from the conditioned medium. We have now determined the partial amino-acid sequence of the purified G-CSF protein, and by using oligonucleotides as probes, have isolated several clones containing G-CSF complementary DNA from the cDNA library prepared with messenger RNA from CHU-2 cells. The complete nucleotide sequences of two of these cDNAs were determined and the expression of the cDNA in monkey COS cells gave rise to a protein showing authentic G-CSF activity. Furthermore, Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G-CSF gene in CHU-2 cells.
Amino Acid Sequence↗
Efficacy of a continuous syringe extraction method for monitoring hemodialysis ultrafiltrate.
The evaluation of hemodialysis ultrafiltrate is essential for the assessment of uremic toxins, dialyzer net performance, protein catabolic rate, and safety and environmental protection. Total dialysate collection (TDC), however, is technically far from the daily procedure used. In the present study, use of a continuous syringe extraction method (CSEM) as a substitute for TDC was tested to determine its comparative effectiveness. Measurements of urea nitrogen, creatinine, phosphate, beta2-microglobulin, and albumin were simultaneously obtained by both TDC and CSEM in 20 dialysis sessions. CSEM showed an extremely significant correlation with TDC for these values. The correlation coefficients were >0.97 for these indicators and the value of Fisher's r to z were all <0.001. Taken together, these data indicate that CSEM is an effective substitute for TDC. With use of CSEM, the evaluation of spent dialysate could become as a daily procedure.
Humans↗
Faecal clearance of alpha 1-antitrypsin reflects disease activity and correlates with rapid turnover proteins in chronic inflammatory bowel disease.
Faecal clearance of alpha 1-antitrypsin was measured in patients with ulcerative colitis and Crohn's disease and compared with disease activity and markers of protein-calorie malnutrition. Patients with active ulcerative colitis and Crohn's disease showed elevated clearance of alpha 1-antitrypsin and clearance declined in most patients with induction of remission. However, even with inactive disease, elevated protein loss persisted in some patients, presumably reflecting residual inflammation in the intestinal mucosa. There was a significant correlation between clearance of alpha 1-antitrypsin and serum levels of retinol-binding protein and transferrin in patients with ulcerative colitis and with retinol-binding protein in patients with Crohn's disease. Clearance of alpha 1-antitrypsin reflects disease activity in inflammatory bowel disease and correlates with serum levels of rapid-turnover proteins such as retinol-binding protein and transferrin, which are markers for the presence of protein-calorie malnutrition.
Adult↗
Fluorographic study on the oxidative stress in the process of gastric mucosal injury: attenuating effect of vitamin E.
In vivo oxidative change was visualized in the gastric mucosa of rats and the alteration was analysed by using a fluorescence microscope equipped with a digital imaging processor during the development of mucosal damage. Dichlorofluorescein (DCF)-associated fluorescence increased after the repeated electrical stimulation on the gastric artery (irritation), suggesting the occurrence of lipid peroxidation. The increase was enhanced in the mid-zone of two adjacent collecting venules. Allopurinol attenuated the oxidative stress in mucosa, showing the involvement of xanthine oxidase. Luminol-dependent chemiluminescence value in the blood taken from gastric vein was elevated by the irritation, suggesting that leucocyte-generated oxygen radicals also participate in this oxidative process. alpha-Tocopherol attenuated both the DCF activation and the increase in chemiluminescence value and prevented gastric mucosal injury. The present results suggest that alpha-tocopherol may be useful for the prevention of oxidative alteration in gastric mucosa.
Allopurinol↗
Regional differences in microvascular response in rat intestine during acute elevation of portal pressure.
The effect of acute elevation of portal pressure on the blood flow of rat intestinal microvessels was studied using a laser Doppler velocimeter and in vivo microscopy. The total intestinal blood flow decreased when portal pressure increased more than +15 cmH2O above the basal value. Blood flow in villus capillaries did not change at portal pressures of +5 to +15 cmH2O, but did decrease at +20 cmH2O. Blood flow in muscle capillaries decreased at all steps of portal hypertension. Red blood cell velocity was decreased by portal hypertension in large venules, but not in small venules of the submucosa. Large venules, but not small venules, dilated in acute portal hypertension. Large arterioles in the submucosa constricted, while small arterioles dilated at portal pressures of +10 to +15 cmH2O. In conclusion, the intestinal microvascular flow response differs according to the degree of portal hypertension and the location on the microvascular tree. Blood flow in villus capillaries and in small submucosal venules is maintained at a small degree of portal hypertension.
Animals↗
Sulfhydryl blocker-induced colitis in the rat: immunological changes in thymus gland and colonic mucosa.
The study was designed to examine the changes of thymus in sulfhydryl blocker-induced colitis. We used N-ethylmaleimide (NEM) as sulfhydryl blockers. Fasted male Sprague-Dawley rats were given 3% NEM in 1% methyl cellulose into the colon. N-ethylmaleimide treatment caused severe diarrhoea with bleeding for the first 7 days. At autopsy, adhesions, colon dilatation, and single or multiple erosions and ulcers were observed. Time-course studies revealed that the lesions were most extensive and severe 3 or 7 days after the administration of NEM. Histological examination of colon on the 3rd day after NEM treatment demonstrated mucosal erosion, oedema and extensive infiltration of neutrophils. The mucosal lesions extended into the submucosa and muscle on the 7th day after NEM treatment. Immunohistochemical studies showed that T cells and macrophages were markedly increased in the lamina propria of colonic mucosa. After 3 weeks, the infiltration of chronic inflammatory cells was observed and regeneration of the mucosa was noticed. The thymus gland was significantly decreased in weight and size on the 3rd day after NEM treatment, but the weight loss of thymus gland was regained in 3 weeks. Transient atrophy of thymus gland was noticed in this colitis model. The phenotypes of thymocytes were not influenced by NEM treatment. It is concluded that the thymus abnormalities in human ulcerative colitis are not induced in this animal model and that other chronic models are necessary for the elucidation of the immunological abnormalities, including thymus abnormalities.
Animals↗
Bile acid-induced depolarization of mitochondrial membrane potential preceding cell injury in cultured gastric mucosal cells.
Changes in energy metabolism elicited by sodium taurocholate and their relation to cell viability were determined in gastric mucosal cells. Cultured mucosal cells were labelled with rhodamine-123, a mitochondrial energization-sensitive fluorescence probe, or by propidium iodide, a fluorochrome which labels the nuclei of non-viable cells. The cells were observed under a fluorescence microscope with a laser scanning confocal imaging system. After the addition of sodium taurocholate at concentrations > 5 mol/L, mucosal cells showed a rapid and significant decrease in rhodamine-123 fluorescence. A decrease to 40% of the pretreated values at 30 min was seen with a concentration of sodium taurocholate of 7.5mmol/L. A marked increase in the percentage of propidium iodide-positive cells was noted when the concentration of sodium taurocholate exceeded 5mmol/L. However, the extent of the decrease in rhodamine-123 fluorescence was always greater than the increase in the percentage of propidium iodide-positive cells, suggesting that most of these gastric mucosal cells remained viable. It is therefore suggested that the decrease in rhodamine-123 fluorescence is largely due to the disturbed oxidative phosphorylation of mitochondria. Pretreatment of gastric mucosal cells with low concentrations of ethanol resulted in a significant cytoprotective effect against sodium taurocholate injury with significant prevention of a decrease in rhodamine-123 fluorescence. It is concluded that sodium taurocholate induces a depolarization of the mitochondrial membrane potential preceding cell injury and that the cytoprotective effect of ethanol relates to its attenuation of the uncoupling effect.
Animals↗
Immunohistochemical study of thymic B cells in myasthenia gravis and ulcerative colitis.
The phenotypes of B cells and dendritic cells in human thymus were examined immunohistochemically using various monoclonal antibodies. Normal thymus contained a few B lymphocytes recognized by CD19, CD20, CD22, L26 and LN-2, which were localized in the medulla. These B cells were negative for LN-1, L30 and CD11c (Leu M5). Activated B cells recognized by CD23 (B6) and L29 antibodies were not present in normal thymus. Dendritic cells stained by CD11c were weakly positive for L26 and CD20. There was no difference in the distribution of dendritic cells between normal thymus and thymus from the patients. In the thymus from patients with myasthenia gravis, numerous B cells were demonstrated in the medullary area and lymphoid follicles. Activated B cells were seen mainly in the germinal center of lymphoid follicles and were scarce in the medulla. Many B cells were also found in the medulla and lymphoid follicles of the thymus from patients with ulcerative colitis. However most of those B cells were not activated, even in the lymphoid follicles. These results suggest that thymic B cells may contribute to the induction of immune abnormalities in patients with myasthenia gravis and those with ulcerative colitis, however, the mechanisms by which thymic B cells participate in the pathogenesis of these two diseases would be different.
B-Lymphocytes↗
gamma-Glutamyl transpeptidase activity in liver of alcoholics and its localization.
The activity and the histochemical localization of gamma-GTP in the liver of chronic alcoholics were investigated. Mean serum gamma-GTP activity in alcoholics was 542.5 +/- 337.9 milliunits/ml, and that of patients with nonalcoholic liver disease was 34.3 +/- 22.6 milliunits/ml. Hepatic gamma-GTP activity in alcoholics was significantly increased compared to that in control patients (15.62 +/- 9.29 versus 4.04 +/- 2.67 units/g of liver; p less than 0.001). A significant correlation was observed between hepatic and serum gamma-GTP activity. Light microscopically, a marked gamma-GTP activity was found in the bile canaliculi and a diffuse activity in the cytoplasm in alcoholic livers. By contrast, in the livers of nonalcoholic patients, only slight activity was observed in the bile canaliculi. The electron micrographs showed the enzyme was localized in the microvilli of both the bile canalicular and plasma membranes and the endoplasmic reticulum near the mitochondria in alcoholics. But a very low activity was demonstrated in the plasma membranes in the livers of nonalcoholic patients.
Bile Canaliculi↗
Cardiac contractile and coronary flow reserves in deoxycorticosterone acetate-salt hypertensive rats.
Cardiac contractility and coronary flow were compared in conscious rats with established deoxycorticosterone acetate-salt hypertension and in those with sham treatment. The hypertensive rats showed a 32% increase in left ventricular/body weight ratio at 9 weeks of treatment and 42% at 18 weeks of treatment. Resting peak rate of change of pressure (dp/dt) was unchanged at 9 weeks and increased at 18 weeks in hypertensive rats, while isoproterenol-stimulated maximal, propranolol-induced minimal, and Ca2+-stimulated maximal peak dp/dt were greater at 18 weeks. These data indicate the preservation of contractile function. At 18 weeks, the beta-adrenergic receptor-mediated contractile reserve, estimated from isoproterenol-stimulated maximal and resting peak dp/dt, was reduced but the propranolol-induced decrease in peak dp/dt was increased in hypertensive rats compared with sham-treated rats. Thus, at this stage, a greater portion of the total contractile capacity appeared to be mobilized with prolongation of hypertension and progression of left ventricular hypertrophy. No differences were observed in left ventricular and right ventricular coronary flow (microspheres) and left ventricular inner/outer flow ratio at rest and with dipyridamole-induced maximal coronary dilatation, at 9 and 18 weeks. There were no alterations in left or right ventricular coronary flow reserves, as estimated from resting and dipyridamole-induced values. The minimal coronary vascular resistance (normalized for gram of tissue) of both the left and right ventricles was increased at either stage, which suggests the occurrence of structural coronary vascular changes. Thus, basal coronary flow and a coronary flow reserve were uncompromised despite evidence of structural coronary vascular alterations in these hypertensive rats.
Analysis of Variance↗